New drug class shows major promise for shrinking nerve tumors

A scientist at Cincinnati Children's who has hunted for decades for ways to shrink the painful and disfiguring nerve tumors caused by neurofibromatosis type 1 (NF1) has made a new breakthrough in the quest.

Nancy Ratner, PhD, and a team of nine co-authors, are reporting that a novel class of medications – known as KRAS inhibitors – shows at least as much potential as FDA-approved MEK inhibitors shrinking NF1 tumors.

Detailed findings, based on tests involving a closely similar line of mice that helped drive early-stage research for MEK inhibitors, were published Sept. 2, 2026, in the journal Science Advances.

These findings provide compelling preclinical evidence for KRAS inhibition as a novel treatment strategy for NF1-associated neurofibromas."

Nancy Ratner, PhD, Cincinnati Children's

What is NF1?

Individuals with neurofibromatosis type 1 develop Schwann cell tumors called neurofibromas that arise within peripheral nerves. NF1 affects about one in every 2,500 to 3,000 newborns. In the United States, about 100,000 to 120,000 people of all ages live with an NF diagnosis.

About 50% of cases trace back to a gene mutation inherited from a parent, while the rest occur after new, random genetic changes. While the mutation is present at birth, the disease is most frequently diagnosed during early childhood, once physical symptoms appear.

Most people who have NF1 experience mild symptoms and live a normal life span. However, tumors that form in the brain, or nerve tumors that block airways or other critical locations can lead to severe health risks, requiring multiple surgeries and other treatments to manage.

Most concerning: the potential for malignant transformation of nerve tumors. About 8% to 13% of patients develop malignant peripheral nerve sheath tumors (MPNSTs), often during adolescence or young adulthood.

As a result of such complications, about 250 people a year in the United States die from NF1.

Cincinnati Children's research helps drive improved NF1 treatments

In recent years, medicines known as MEK inhibitors have helped reduce NF1 tumor sizes for many patients. Two MEK inhibitors– selumetinib (2020) and mirdametinib (2025) – were approved by the FDA in significant part thanks to Ratner's early research. Her team developed a crucial mouse model that mimicked the human disease well enough to show the potential value of MEK inhibitors.

Ratner has worked ever since to further understand the biology of NF1 tumors and search for even more effective treatments. In fact, she was recognized in 2024 by the NF Forward foundation for her career-long dedication to NF1 research.

Now, her team has achieved a new level of progress against these nerve tumors.

Proof-of-concept findings for KRAS inhibitors

Using their genetically engineered Dhh-Cre;Nf1^fl/fl mouse models, the researchers demonstrated that the KRAS protein, which normally acts like an on/off switch to manage nerve growth, plays a dominant role in tumor formation when Schwann cells lack the Nf1 gene. This suggested that blocking KRAS might also be used to treat tumors.

The team then showed that giving the mice twice-daily doses of an oral KRAS inhibitor called BI6674 reduced neurofibroma burden while changing how immune cells behaved in the tumor microenvironment. The tumor reduction impact was at least as strong as that generated by MEK inhibitors. However, because the new medication acts against a different place in the disease pathway, it may pose less severe set of side effects.

These findings suggest that KRAS inhibitors might serve as an alternative treatment for people who react poorly to MEK inhibitors, or even as a replacement for MEK inhibitors. But perhaps more important, for those who can tolerate combined therapy, the resulting one-two punch may become a decisive treatment for NF1.

"The Dhh-Cre;Nf1^fl/fl mouse model we developed faithfully recapitulates human plexiform neurofibroma biology," Ratner says. "The translational value of this system was demonstrated when these mice successfully predicted the clinical benefit of MEK inhibitors."

While MEK inhibitors have provided useful pharmaceutical treatment for NF1 tumors, the benefits have been limited. About 30% of patients show no response to MEK inhibition and tumor shrinkage rate is rarely greater than 20%. Meanwhile, maintaining tumor control requires continuous therapy that comes with potential dose-limiting toxicities.

"These limitations highlight a critical need for alternative therapeutic strategies," Ratner says.

By comparison, examining nerve roots, dorsal root ganglia, and peripheral nerves in mice treated with the KRAS inhibitor revealed no hypertrophy, hyperplasia, or tumor formation, not even in old mice (25–30 months of age).

Next steps

Human clinical trials will be needed to verify the benefits of KRAS inhibition for treating NF1. Optimal dosing schedules, especially for growing children, remain to be determined. Likewise, it is not clear how long treatment benefits might last in people vs the mice.

Meanwhile, the BI6674 inhibitor used in this study may not be the only or best inhibitor to use in people. The research team plans to further test other KRAS inhibitors that have emerged in recent years.